Assessing the potential molecular mechanism of arsenite-induced skin cell senescence

Sufei Du; Fan Yang; Liping Wu; Dexiu Hu; Yuhong Zhang; Maoyuan Gong; Yang Yang; Xingcan Yang; Qibing Zeng

doi:10.1093/toxres/tfad075

Assessing the potential molecular mechanism of arsenite-induced skin cell senescence

Toxicol Res (Camb). 2023 Sep 9;12(5):843-852. doi: 10.1093/toxres/tfad075. eCollection 2023 Oct.

Authors

Sufei Du¹, Fan Yang¹, Liping Wu¹, Dexiu Hu¹, Yuhong Zhang¹, Maoyuan Gong¹, Yang Yang¹, Xingcan Yang¹, Qibing Zeng^{1

2}

Affiliations

¹ Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education & School of Public Health, Guizhou Medical University, Dongqing Road 2, Guiyang 550025, China.
² Guizhou Provincial Engineering Research Center of Food Nutrition and Health, School of Public Health, Guizhou Medical University, Dongqing Road 2, Guiyang 550025, China.

PMID: 37915474
PMCID: PMC10615813 (available on 2024-09-09)
DOI: 10.1093/toxres/tfad075

Abstract

Arsenic exposure is a public health concern worldwide. Skin damage, as a typical lesion of arsenic exposure, the mechanism is still unknown. Studies have found that cellular senescence plays a key role in arsenic-induced skin damage, and the previous research found that the ERK/CEBPB signaling pathway may be an important molecular event of arsenic-induced skin cell senescence, but its specific mechanism is unknown. In this study, genetic engineering technology was used to construct stable HaCaT cell lines, and the role and mechanism of ERK/CEBPB signaling pathway in arsenic-induced HaCaT cell senescence were verified by knockdown and overexpression of ERK and CEBPB in both forward and backward. It was found that knockdown of CEBPB or ERK can downregulate the ERK/CEBPB signaling pathway and reduce arsenic-induced skin cell senescence. In contrast to knockdown, overexpression of CEBPB or ERK can upregulate the ERK/CEBPB signaling pathway and aggravate the senescence of skin cells caused by arsenic. These findings suggest that sodium arsenite can further promote SASP secretion and the expression of p53, p21 and p16 ^INK4a by activating the ERK/CEBPB signaling pathway, induce cell cycle arrest and trigger cellular senescence.

Keywords: CEBPB; ERK; SASP; arsenic; senescence.